OBJECTIVE: To elucidate the mechanisms governing the hepatic disposition of drugs and chemical carcinogens. This includes uptake, binding, metabolism and biliary excretion of these compounds. APPROACH: The substances to be studied are administered to rats or added to an isolated liver perfusion. Their pharmacokinetics are then determined from rates of plasma disappearance, liver concentrations and biliary excretion. The capacity of the liver to metabolize these compounds is studied in vitro and extrapolations are then made as to the controlling influence of metabolism on the binding and excretion processes. Nafenopin, a potent hypolipidemic agent, has been shown to stimulate liver growth, to produce choleresis and to block the hepatic uptake of a number of drugs and carcinogens. It is being used as a tool to investigate hepatic excretory functions.